Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients: A pilot study

Giorgio Aquila, Cinzia Fortini, Antonio Pannuti, Serena Delbue, Micaela Pannella, Marco Bruno Morelli, Cristiana Caliceti, Fausto Castriota, Monica Mattei, Alessia Ongaro, Agnese Pellati, Pasquale Ferrante, Lucio Miele, Luigi Tavazzi, Roberto Ferrari, Paola Rizzo, Alberto Cremonesi

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p,146-5p, 155-5p, 424-5p. We found an "inflamed plaque" gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a "stable plaque" profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics. Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.

Original languageEnglish (US)
Article number98
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
StatePublished - May 4 2017
Externally publishedYes

Keywords

  • Inflammation
  • Macrophages
  • MicroRNA
  • Notch
  • Peripheral artery disease
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients: A pilot study'. Together they form a unique fingerprint.

  • Cite this

    Aquila, G., Fortini, C., Pannuti, A., Delbue, S., Pannella, M., Morelli, M. B., Caliceti, C., Castriota, F., Mattei, M., Ongaro, A., Pellati, A., Ferrante, P., Miele, L., Tavazzi, L., Ferrari, R., Rizzo, P., & Cremonesi, A. (2017). Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients: A pilot study. Journal of Translational Medicine, 15(1), [98]. https://doi.org/10.1186/s12967-017-1199-3